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The emergence of collective cell behaviors from intercellular interactions

Award Number: R01HD105009
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/24/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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The emergence of collective cell behaviors from intercellular interactions - Project Summary Embryos and organs are shaped by complex collective cell movements involving the coordinated action of thousands of cells over space and time. Impairments in collective cell motion underlie many structural birth defects, the most common of which is the failure to close the neural tube leading to spina bifida, exencephaly, or most severely craniorachischisis. One of the key challenges in developmental biology and tissue engineering is understanding the molecular mechanisms by which cells coordinate their behaviors across thousands of cells to generate large-scale changes in tissue forms through local changes in subcellular organization. The planar cell polarity pathway (PCP) has emerged as a key regulator that organizes individual cell behaviors into large-scale collective cell movements, and is essential for the proper formation of most organ systems in vertebrates. Given the diversity of structures whose morphogenesis relies on PCP, a central challenge is to define a common, unifying set of molecular principals through which PCP acts. Specifically, the molecular links between PCP components and their downstream effectors are poorly defined. Moreover, we do not understand how polarity within individual cells is coordinated into collective, tissue-scale behaviors. Defining these molecular links in detail and connecting them to higher order patterns of collective cell behavior is thus crucial to our basic understanding of tissue morphogenesis. The murine epidermis displays striking spatial and directional patterns, and is an ideal model system to approach these questions. Using newly developed live imaging capabilities, we recently discovered two novel collective cell movements during formation of epithelial placodes in the mammalian skin. These movements bear resemblance to the behaviors that underlie embryonic germ layer formation and gastrulation, suggesting that deeply conserved mechanisms underlie the morphogenesis of very diverse structures. We propose to use the power of the murine epidermis to gain a molecular understanding of these Wnt and PCP-dependent collective cell movements. Specific Aim 1 will define the mechanisms of PCP-mediated force generation and symmetry breaking that drive collective cell motion. Specific Aim 2 will elucidate how patterns of differential cell adhesion promote epithelial motility and prevent cell mixing to compartmentalize collective epithelial movements. Specific Aim 3 will decipher the mechanisms driving epithelial rearrangements during periodic pattern formation. Our findings will define how local, intercellular interactions generate the large-scale collective movements that occur during organogenesis and reveal how structural birth defects arise when these processes go awry.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $416,091 )
2025	2025	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Child Health and Human Development Extramural Research	000	4	5/2/2025	NON-COMPETING CONTINUATION	$416,091
														Subtotal = $416,091

Issue Date FY: 2024 ( Subtotal = $411,930 )
2024	2024	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Child Health and Human Development Extramural Research	000	3	6/5/2024	NON-COMPETING CONTINUATION	$411,930
														Subtotal = $411,930

Issue Date FY: 2023 ( Subtotal = $416,091 )
2023	2023	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Child Health and Human Development Extramural Research	000	2	5/2/2023	NON-COMPETING CONTINUATION	$416,091
														Subtotal = $416,091

Issue Date FY: 2022 ( Subtotal = $416,091 )
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Child Health and Human Development Extramural Research	000	1	6/24/2022	NEW	$416,091
														Subtotal = $416,091

Grand Total All Awards = $1,660,203

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The emergence of collective cell behaviors from intercellular interactions

Award Number: R01HD105009

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/24/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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